title: Effects of the selective estrogen receptor modulator ospemifene on bone in rats.
abstract: Ospemifene is a non-estrogen agent that exerts tissue-specific estrogen agonistic and weak antagonistic effects (i. e., is a selective estrogen receptor modulator [SERM]). The effects of various once-daily oral doses of ospemifene on bone are examined across 3 studies for 4 or 52 weeks after surgery in the ovariectomized (OVX) rat model of postmenopausal bone loss. Ospemifene treatment reduced the loss of bone mineral content and density observed in untreated OVX rats, significantly increased distal femur bone mineral content at 51 weeks at 25 mg/kg dose compared with untreated OVX rats (p<0.01), and significantly increased trabecular bone mineral density of the distal femur and proximal tibia with 1, 5, or 25 mg/kg doses after 52 weeks. Ospemifene 5 and 25 mg/kg preserved distal femur trabecular structure; trabecular number was significantly increased, whereas trabecular separation and eroded surface values were significantly decreased (all p<0.01). Structural changes associated with ospemifene were accompanied by increased mechanical strength of femurs and 4th lumbar vertebra compared with untreated OVX rats. Ospemifene 10 mg/kg prevented OVX-induced bone loss; trabecular bone volume of distal femurs was increased after 4 weeks. Further, histomorphometric measures revealed decreased bone resorption after 4 weeks of ospemifene treatment, with effects similar to other SERMs (raloxifene and droloxifene). Ospemifene 3 and 10 mg/kg significantly inhibited OVX-induced increases in osteoclast number, and doses ≥0.3 mg/kg dose-dependently reversed the OVX-induced increase in the double-labeled volume:bone volume ratio. These results demonstrate antiresorptive, selective agonist effects of ospemifene on bone that appear similar to raloxifene in this in vivo animal model of estrogen deficiency.
authors.affiliation: Hormos Medical Ltd., Turku, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Kangas
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Härkönen
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Väänänen
authors.affiliation: Pharmatest Ltd., Turku, Finland.
authors.forename: Z
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D002452:Cell Count; D019245:Compressive Strength / Q000187:drug effects; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D008159:Lumbar Vertebrae / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D013977:Tibia / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D007986:Luteinizing Hormone; C119141:Ospemifene